Dry powder inhaler with aeroelastic dispersion mechanism

ABSTRACT

A dry powder inhaler for delivering medicament to a patient includes a housing defining a chamber for receiving a dose of powdered medicament, an inhalation port in fluid communication with the chamber, at least one airflow inlet providing fluid communication between the chamber and an exterior of the housing, and an aeroelastic element in the chamber and associated with a dose of powdered medicament. A tensioning assembly is configured to apply a first amount of tension to the aeroelastic element such that the aeroelastic element is capable of vibrating in response to airflow through the chamber so as to aerosolize the dose of powdered medicament.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.11/713,180, entitled “Dry Powder Inhaler with Aeroelastic DispersionMechanism,” filed on Mar. 2, 2007, pending, which claims the benefit ofpriority of U.S. provisional application No. 60/778,878, entitled “DryPowder Inhaler with Aeroelastic Dispersion Mechanism,” filed on Mar. 3,2006, the contents of both of which are incorporated herein by referencein their entirety.

TECHNICAL FIELD

The present invention is directed generally to inhalers, for example,dry powder inhalers, and methods of delivering a medicament to apatient. More particularly, the present invention is directed to drypowder inhalers having an aeroelastic dispersion mechanism.

BACKGROUND

Dry powder inhalers (“DPIs”) represent a promising alternative topressurized meted dose inhaler (“pMDI”) devices for delivering drugaerosols without using CFC propellants. See generally, Crowder et al.,2001: an Odyssey in Inhaler Formulation and Design, PharmaceuticalTechnology, pp. 99-113, July 2001; and Peart et al., New Developments inDry Powder Inhaler Technology, American Pharmaceutical Review, Vol. 4,n,3, pp. 37-45 (2001). Martonen et al. 2005 Respiratory Care, Smyth andHickey American Journal of Drug Delivery, 2005.

Typically, the DPIs are configured to deliver a powdered drug or drugmixture that includes an excipient and/or other ingredients.Conventionally, many DPIs have operated passively, relying on theinspiratory effort of the patient to dispense the drug provided by thepowder. Unfortunately, this passive operation can lead to poor dosinguniformity since inspiratory capabilities can vary from patient topatient, and sometimes even use-to-use by the same patient, particularlyif the patient is undergoing an asthmatic attack or respiratory-typeailment which tends to close the airway.

Generally described, known single and multiple dose DPI devices use: (a)individual pre-measured doses, such as capsules containing the drug,which can be inserted into the device prior to dispensing; or (b) bulkpowder reservoirs which are configured to administer successivequantities of the drug to the patient via a dispensing chamber whichdispenses the proper dose. See generally, Prime et al., Review of DryPowder Inhaler's, 26 Adv. Drug Delivery Rev., pp. 51-58 (1997); andHickey et al., A New Millennium for Inhaler Technology, 21 Pharm. Tech.,n. 6, pp. 116-125 (1997).

In operation, DPI devices desire to administer a uniform aerosoldispersion amount in a desired physical form (such as a particulatesize) of the dry powder into a patient's airway and direct it to adesired deposit site. If the patient is unable to provide sufficientrespiratory effort, the extent of drug penetration, especially to thelower portion of the airway, may be impeded. This may result inpremature deposit of the powder in the patient's mouth or throat.

A number of obstacles can undesirably impact the performance of the DPI.For example, the small size of the inhalable particles in the dry powderdrug mixture can subject them to forces of agglomeration and/or cohesion(i.e., certain types of dry powders are susceptible to agglomeration,which is typically caused by particles of the drug adhering together),which can result in poor flow and non-uniform dispersion. In addition,as noted above, many dry powder formulations employ larger excipientparticles to promote flow properties of the drug. However, separation ofthe drug from the excipient, as well as the presence of agglomeration,can require additional inspiratory effort, which, again, can impact thestable dispersion of the powder within the air stream of the patient.Unstable dispersions may inhibit the drug from reaching its preferreddeposit/destination site and can prematurely deposit undue amounts ofthe drug elsewhere.

A number of different inhalation devices have been designed to attemptto resolve problems attendant with conventional passive inhalers. Forexample, U.S. Pat. No. 5,655,523 discloses and claims a dry powderinhalation device which has a deagglomeration-aerosolization plunger rodor biased hammer and solenoid. U.S. Pat. No. 3,948,264 discloses the useof a battery-powered solenoid buzzer to vibrate the capsule toeffectuate the efficient release of the powder contained therein. Thosedevices are based on the proposition that the release of the dry powdercan be effectively facilitated by the use of energy input independent ofpatient respiratory effort.

U.S. Pat. No. 5,533,502 to Piper discloses and claims a powder inhalerusing patient inspiratory efforts for generating a respirable aerosol.The Piper invention also includes a cartridge capable of rotating,holding the depressed wells or blisters defining the medicament holdingreceptacles. A spring-loaded carriage compresses the blister againstconduits with sharp edges that puncture the blister to release themedication that is then entrained in air drawn in from the air inletconduit so that aerosolized medication is emitted from the aerosoloutlet conduit.

Crowder et al. describe a dry powder inhaler in U.S. Pat. No. 6,889,690comprising a piezoelectric polymer packaging in which the powder foraerosolization is simulated using non-linear signals determined a priorifor specific powders.

In recent years, dry powder inhalers (DPIs) have gained widespread use,particularly in the United States. Currently, the DPI market isestimated to be worth in excess of $4 billion. Dry powder inhalers havethe added advantages of a wide range of doses that can be delivered,excellent stability of drugs in powder form (no refrigeration), ease ofmaintaining sterility, non-ozone depletion, and they require nopress-and-breathe coordination.

There is great potential for delivering a number of therapeuticcompounds via the lungs (see, for example, Martonen T., Smyth H D C,Isaccs K., Burton R., “Issues in Drug Delivery: Dry Powder InhalerPerformance and Lung Deposition”: Respiratory Care. 2005, 50(9); andSmyth H D C, Hickey, A J, “Carriers in Drug Powder Delivery:Implications for Inhalation System Design,” American Journal of DrugDelivery, 2005, 3(2),117-132). In the search for non-invasive deliveryof biologics (which currently must be injected), it was realized thatthe large highly absorptive surface area of the lung with low metabolicdrug degradation, could be used for systemic delivery of proteins suchas insulin. The administration of small molecular weight drugspreviously administered by injection is currently under investigationvia the inhalation route either to provide non-invasive rapid onset ofaction, or to improve the therapeutic ratio for drugs acting in the lung(e.g. lung cancer).

Gene therapy of pulmonary disease is still in its infancy but couldprovide valuable solutions to currently unmet medical needs. Therecognition that the airways may provide a real opportunity fordelivering biotech therapeutics in a non-invasive way was recentlyachieved with Exubera™, an inhaled insulin product. This product hasobtained a recommendation for approval by US Food and DrugAdministration and will lead to expanded opportunities for otherbiologics to be administered via the airways.

Key to all inhalation dosage forms is the need to maximize the“respirable dose” (particles with aerodynamic diameters<5.0 μm thatdeposit in the lung) of a therapeutic agent. However, bothpropellant-based inhalers and current DPI systems only achieve lungdeposition efficiencies of less than 20% of the delivered dose. Theprimary reason why powder systems have limited efficiency is thedifficult balancing of particle size (particles under 5 μm diameter) andstrong inter-particulate forces that prevent deaggregation of powders(strong cohesive forces begin to dominate at particle sizes<10 μm)(Smyth H D C., Hickey, A J., “Carriers in Drug Powder Delivery:Implications for inhalation System Design,” American Journal of DrugDelivery, 2005, 3(2), 117-132). Thus, DPIs require considerableinspiratory effort to draw the powder formulation from the device togenerate aerosols for efficient lung deposition (see FIG. 1 for anillustration of typical mechanism of powder dispersion for DPIs). Manypatients, particularly asthmatic patients, children, and elderlypatients, which are important patient groups for respiratory disease,are not capable of such effort. In most DPIs, approximately 60 L/min ofairflow is required to effectively deaggregate the fine cohesive powder.All currently available DPIs suffer from this potential drawback.

Multiple studies have shown that the dose emitted from dry powderinhalers (DPI) is dependent on air flow rates (see Martonen T., Smyth HD C, Isaccs K., Burton R., “Issues in Drug Delivery: Dry Powder InhalerPerformance and Lung Deposition”: Respiratory Care. 2005, 50(9)).Increasing air-flow increases drug dispersion due to increases in dragforces of the fluid acting on the particle located in the flow. TheTurbuhaler® device (a common DPI), is not suitable for children becauseof the low flow achieved by this patient group (see Martonen T., Smyth HD C, Isaccs K., Burton R., “Issues in Drug Delivery: Dry Powder InhalerPerformance and Lung Deposition”: Respiratory Care. 2005, 50(9)).

Considerable intra-patient variability of inhalation rates has beenfound when patients inhale through two leading DPI devices. Thatinherent variability has prompted several companies to evaluate ways ofproviding energy in the inhaler (i.e. “active” DPIs). Currently, thereis no active DPI commercially available. The active inhalers underinvestigation include technologies that use compressed air,piezoelectric actuators, and electric motors. The designs of thoseinhalers are very complex and utilize many moving parts and components.The complexity of those devices presents several major drawbacksincluding high cost, component failure risk, complex manufacturingprocedures, expensive quality control, and difficulty in meetingspecifications for regulatory approval and release (Food and DrugAdministration).

Alternatively, powder technology provides potential solutions for flowrate dependence of DPIs. For example, hollow porous microparticleshaving a geometric size of 5-30 μm, but aerodynamic sizes of 1-5 μmrequire less power for dispersion than small particles of the same mass.This may lead to flow independent drug dispersion but is likely to belimited to a few types of drugs with relevant physicochemicalproperties.

Thus there are several problems associated with current dry powderinhaler systems including the most problematic issue: the dose a patientreceives is highly dependent on the flow rate the patient can drawthrough the passive-dispersion device. Several patents describingpotential solutions to this problem employ an external energy source toassist in the dispersion of powders and remove this dosing dependence onpatient inhalation characteristics. Only one of these devices has madeit to market or been approved by regulatory agencies such as the US Foodand Drug Administration. Even upon approval, it is likely that thesecomplex devices will have significant costs of manufacture and qualitycontrol, which could have a significant impact on the costs of drugs topatients.

The present disclosure describes exemplary dry powder inhalers andassociated single or multi-dose packaging, which holds the compound tobe delivered for inhalation as a dry powder. These dry powder inhalersbridge the gap between passive devices and active devices. The inhalersare passive devices that operate using the energy generated by thepatient inspiratory flow inhalation maneuver. However, the energygenerated by airflow within the devices is focused on the powder byusing oscillations induced by airflow across an aeroelastic element. Inthis way the inhalers can be “tuned” to disperse the powder mostefficiently by adjusting the resonance frequencies of the elasticelement to match the physicochemical properties of the powder. Inaddition, the airflow rate required to generate the appropriateoscillations within the device is minimized because some of the energyused to create the vibrations in the elastic element is pre-stored inthe element in the form of elastic tension (potential energy). Inhalerperformance may be tailored to the lung function of individual patientsby modulating the elastic tension. Thus, even patients with poor lungfunction and those who have minimal capacity to generate airflow duringinspiration will able to attain the flow rate required to induceoscillations in the elastic element.

SUMMARY OF THE INVENTION

An exemplary embodiment of the invention comprises a dry powder inhalerwith an integrated assisted dispersion system that is adjustableaccording to the patients' inspiratory capabilities and theadhesive/cohesive nature of the powder. The inhaler comprises anaeroelastic element that flutters or oscillates in response to airflowthrough the inhaler. The aeroelastic element provides concentratedenergy of the airflow driven by the patient into the powder to bedispersed. The aeroelastic element is preferably a thin elastic membraneheld under tension that reaches optimal vibrational response at low flowrates drawn through the inhaler by the patient. The aeroelastic elementis preferably adjustable according to the patient's inspiratorycapabilities and the adhesive/cohesive forces within the powder fordispersal.

According to various aspects of the disclosure, a dry powder inhaler fordelivering medicament to a patient includes a housing defining a chamberfor receiving a dose of powdered medicament, an inhalation port in fluidcommunication with the chamber, at least one airflow inlet providingfluid communication between the chamber and an exterior of the housing,and an aeroelastic element in the chamber and associated with a dose ofpowdered medicament. A tensioning assembly is configured to apply afirst amount of tension to the aeroelastic element such that theaeroelastic element is capable of vibrating in response to airflowthrough the chamber so as to aerosolize the dose of powdered medicament.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates airflow across an aeroelastic element in accordancewith various aspects of the disclosure.

FIG. 2 illustrates airflow past an airflow modifier and across anaeroelastic element in accordance with various aspects of thedisclosure.

FIG. 3A is a schematic representation of a top cross-sectional view ofan exemplary inhaler in accordance with various aspects of thedisclosure.

FIG. 3B is a schematic representation of an end cross-sectional view ofan exemplary inhaler in accordance with various aspects of thedisclosure.

FIG. 4 is a schematic representation of first and second rollers loadedwith the aeroelastic membrane with axles in the center of the rollers inaccordance with various aspects of the disclosure.

FIG. 5 is representation of an exemplary dosing applicator in accordancewith various aspects of the disclosure.

FIG. 6 is a representation of another exemplary dosing applicator inaccordance with various aspects of the disclosure.

FIGS. 7A-7C are representations of an exemplary aeroelastic membrane andits relation to exemplary base clamps, upper clamps, and tensioning rodsin accordance with various aspects of the disclosure.

FIG. 8 is a representation of an exemplary dispensing mechanism inaccordance with various aspects of the disclosure.

FIG. 9 is a representation of an alternative exemplary dispensingmechanism in accordance with various aspects of the disclosure.

FIG. 10 is a representation of an alternative exemplary dispensingmechanism in accordance with various aspects of the disclosure.

DETAILED DESCRIPTION

An exemplary embodiment of a dry powder inhaler 100 is illustrated inFIGS. 3A and 3B. According to various aspects of the disclosure, the drypowder inhaler 100 may comprise a casing 102 having an outer wall 104and two inner walls 106, 108. The inner walls 106, 108 may extend in afirst direction from a first inner surface 112 of the outer wall 104toward a second inner surface 114 of the outer wall 104. The inner walls106, 108 may also extend in a second direction from a proximal end 116of the casing 102 to a distal end 118 of the casing 102. Thus, accordingto various aspects, the outer wall 104 and inner walls 106, 108 maycooperate to define three chambers in the casing 102.

According to some aspects, the three chambers may include a middlechamber 122 and two side chambers 124, 126 located on opposite sides ofthe middle chamber 122 relative to one another. The side chambers maycomprise a first side chamber 124 located to a first side of the middlechamber 122 and a second side chamber 126 located to a second side ofthe middle chamber 122.

In accordance with various aspects, the distal end 118 of the casing 102may include one or more airflow inlets 128 providing fluid communicationbetween the middle chamber 122 and ambient air outside the casing 102.The proximal end 116 of the casing 102 may include a mouthpiece 130. Themouthpiece 130 may a separate structure affixed to the outer wall 104 ofthe casing 102, or the mouthpiece 130 and casing 102 may comprise asingle piece of unitary construction. The mouthpiece 130 may include anopening 132 providing fluid communication between the middle chamber 122and the outside of the casing 102. The opening 132 may be shaped as anoval, a circle, a triangle, or any other desired shape. The mouthpiece130 may have a shape that facilitates pursing of a patient's lips overthe mouthpiece 130 and creating a seal between the lips and themouthpiece 130.

The inhaler 100 may include a nozzle 134 between the middle chamber 122and the opening 132. According to various aspects, the nozzle 134 mayextend from the opening 132, through the mouthpiece 130, and into themiddle chamber 122. In some aspects, the nozzle 134 may comprise atleast one helical tube 136 through which air and powder can be inhaled.The tube 136 can be configured to increase the turbulence in the airthat flows through the nozzle 134.

An aeroelastic element 140 may extend across a center region 142 of themiddle chamber 122 between the inner walls 106, 108. The aeroelasticelement 140 may include one or more doses of a medicament 141, forexample, doses of powdered medicament, and the center region 142 maycomprise a region for dispensing a dose of medicament into airflowthrough the inhaler 100. According to some aspects, the aeroelasticelement 140 may comprise a membrane 144, for example, a thin elasticmembrane, wound between two spools 146, 148. An unused end of themembrane 144 may be wound on a first spool 146, and a used end of themembrane 144 may be wound on a second spool 148. The first spool 146 maybe disposed about a first axle 147, and the second spool 148 may bedisposed about a second axle 149. The first spool 146 may be in thefirst side chamber 124, and the second spool 148 may be in the secondside chamber 126. In such an embodiment, the membrane 144 extendsthrough a slot 150 in the inner wall 106, across the center region 142,and through a slot 152 in the inner wall 108. In accordance with someaspects, the aeroelastic element 140 may comprise a membrane, a film, areed, a sheet, a panel, or a blade. The aeroelastic element may bemanufactured of materials comprising polymers, thin metals,polymer-coated metals, and/or metal-coated polymers.

According to various aspects, the inhaler 100 may include two baseclamps 154, 156 fixedly attached to a first inner surface 112 of thecasing 102. According to some aspects, the base clamps 154, 156 may bein the middle chamber 122. A first of the base clamps 154 may be betweenthe center region 142 and the first inner wall 106, and the second ofthe base clamps 156 may be between the center region 142 and the secondinner wall 108. The aeroelastic element 140 may rest on the base clamps154, 156. The inhaler 100 may include two upper clamps 158, 160 in themiddle chamber 122 associated with the two base clamps 154, 156. Forexample, a first upper clamp 158 may be on an opposite side of theaeroelastic element 140 relative to the first base clamp 154 andconfigured to descend atop the first base clamp 154 to sandwich theaeroelastic element therebetween. Similarly, the second upper clamp 160may be on an opposite side of the aeroelastic element 140 relative tothe second base clamp 156 and configured to descend atop the second baseclamp 156 to sandwich the aeroelastic element therebetween. The upperclamps 158, 160 and base clamps 154, 156 may hold the aeroelasticelement 140 in place across the center region 142 with a desired amountof tension. The desired amount of tension may be determined based on auser's inhalation strength. It should be appreciated that in someaspects, the upper clamps may be fixedly attached to the second innersurface 114 of the casing 102, and the base clamps may be configured toascend toward the upper clamps to sandwich the aeroelastic elementtherebetween.

In an alternative embodiment (not shown), a first of the base clamps 154may be in the first side chamber 124 between the first spool 146 and thefirst wall 106, and the second of the base clamps 156 may be in thesecond side chamber 126 between the second spool 148 and the second wall108.

The inhaler 100 may include an advancement member 162 extending outwardof the casing 102. The advancement member 162 may comprise, for example,a lever, a dial, or the like. The advancement member 162 may bemechanically coupled to the first and second upper clamps 158, 160 via,for example, a crank 164 or other known linkage. The advancement member162 and crank 164 are structured and arranged such that when theadvancement member 162 is actuated by a user, the crank 164 is caused tomove the upper clamps 158, 160 in a direction away from the base clamps154, 156. Actuation of the advancement member 162 may also cause thesecond axle 149 to turn in a manner that increases the used end of theaeroelastic element 140 wound thereon.

According to some exemplary aspects, as shown in FIGS. 7A-7C, theinhaler 100 may include one or more tensioning rods 166, 168 configuredto increase the tension of the aeroelastic element 140 beyond thetension applied by the base clamps 154, 156 and upper clamps 158, 160.The tensioning rods 166, 168 are between the first and second upperclamps 158, 160. The tensioning rods 166, 168 may be mechanicallycoupled to the crank 164 such that actuation of the advancement member162 causes the tensioning rods 166, 168 to move in a direction away fromthe aeroelastic element 140. When the advancement member 162 is releasedor unactuated, the tensioning rods 166, 168 return to a position thatapplies a desired amount of tension to the aeroelastic element 140. Itshould be appreciated that in some aspects, one or more tensioncontrollers 157, 159 (FIG. 4) may be attached to one or both of thespool axles 147, 149, thus allowing the tension of the aeroelasticelement 140 to be manually fixed and maintained across the spool axles147, 149 and obviating the need for tensioning rods. In any design, theamount tension applied by the clamps, tensioning rods, and/or tensioncontrollers can be determined based on inhalation strength of a user.

Referring again to FIG. 3B, in various aspects, the second axle 149associated with the second spool 148 may comprise a concentric spring170, which is mechanically coupled to the advancement member 162 so thatactuation of the advancement member 162 results in the aeroelasticelement 140 being transferred from the first spool 138 to the secondspool 148 as the spring-loaded axle 149 is activated. The inhaler 100may include a roller 172 (FIG. 5) adjacent to the first spool 146 andengaging the aeroelastic element 140, thereby resulting in additionaltension in the aeroelastic element.

According to some aspects, for example, inhalers having an aeroelasticelement with multiple doses of medicament, a dose counter 174 may bemechanically coupled to the advancement member 162 in such a way thatthe dose counter 174 changes numbers by one each time the advancementmember 162 is actuated. In some aspects, the dose counter 174 may be atan exterior surface of the casing 102 so as to be visible to a user. Insome aspects, the dose counter 174 may be inside the casing 102, butvisible to a user via a transparent or translucent window (not shown),as would be understood by persons skilled in the art.

According to various aspects, as shown in FIG. 5, the inhaler 100 mayinclude a powder dose applicator 176 located between the first spool 146and the first base clamp 154. In some aspects, the powder doseapplicator 176 may include a dispensing chute 178 filled with at leastone dose of powder 180. The dispensing chute 178 may include a top end182 and a bottom end 184. A wheel 186 may be at the bottom end of thedispensing chute 178. The wheel 186 may be rotatable about an axle 188.The axle 188 may be mechanically coupled to the advancement member 162such that the wheel 186 rotates an amount sufficient to dispense onedose of powdered medicament to the aeroelastic element. For example, thewheel 186 may include one or more notches 190 in its periphery, with thevolume of each notch being sized for one dose of powdered medicament.

According to some aspects, the wheel shown in FIG. 5 may be replacedwith a dispensing disk 686, as shown in FIG. 6. For example, thedispensing chute 178 above the aeroelastic element 140 is filled with atleast one dose of powdered medicament. The dispensing disk 686 may belocated between the aeroelastic element 140 and the dispensing chute 178and may be in contact with the bottom end 184 of the chute 178. The disk686 may further include multiple dispensing openings 690 clustered inone section of the disk 686, for example, a periphery of the disk 686.The dispensing openings 690 correspond to an accurate amount of powderedmedicament to be dispensed as a dose. The dispensing disk 686 rotatesabout an axle 688 as the advancement member 162 is actuated, therebyresulting in an accurate amount of powdered medicament falling throughthe dispensing openings 690 and to the aeroelastic element 140. Forexample, the disk 686 may make one complete 360° rotation each time theadvancement member 162 is actuated.

In various aspects, the inhaler 100 may include blister strip packagingattached to the two spools in place of the powder dose applicatorsdiscussed above. For example, as shown in FIG. 8, the blister strippackaging 801 may include at least one individual dosing cup 803. Eachcup 803 may be filled with a dose of powdered medicament and covered bya peelable top layer. The dosing cups 803 may be arranged serially alongthe length of the packaging strip 801. An aeroelastic element 840 may bestretched across the center region 142 and fixedly coupled to, forexample, the inner walls or any other structure capable of maintainingthe element 840 fixedly stretched across the center region 142. Thestrip 801 may be in proximity to the aeroelastic element 840 in thecenter region 142 such that the aeroelastic element 840 may act as anactuator, making contact with the blister packaging and dispersing thepowder dose when the aeroelastic element begins to vibrate duringinhalation by a patient. A powder dose opener 805 may be configured toremove the top peelable layer from the blister strip packaging 801 forone dose when the blister strip 801 is advanced from the first spool tothe second spool. The powder dose opener may alternatively be a simplepuncturing device, such as a needle, that inserts small holes in theblister strip blister cavity, making the dose ready for inhalation.

In some embodiments, as shown in FIG. 9, blister strip packaging 901 mayinclude clusters 905 of multiple small dosing cups 903 for simultaneousmultiple drug dosing, the clusters 905 may be arranged serially alongthe length of the blister strip 901. The large arrows depict thedirection of airflow across the blister strip and aeroelastic element.The small vertical arrows depict the vibrational motion of theaeroelastic element. In various embodiments, as shown in FIG. 10, theinhaler may include an aeroelastic element 1040 that may comprise, forexample, an aeroelastic and deformable membrane. The element 1040 mayinclude at least one individual dosing cup 1003 filled with a dose ofpowdered medicament in the form of blister strip packaging 1001. Thedosing cup 1003 may be configured to deform and raise the powder dose tothe level of the surrounding element 1040.

It should be appreciated that the inhaler may comprise a single powderdose such that the inhaler may be disposed of after a single use.

Referring again to FIG. 5, in some aspects, the inhaler 100 may includetwo rollers 192, one above and one below the aeroelastic element 140.The rollers 192 may be between the powder dose applicator 176 and thefirst base clamp 154 or between the powder dose applicator 176 and theinner wall 106. The rollers 192 turn as the aeroelastic element 140moves from the first spool 146 to the second spool 148 due to thefrictional force applied by the aeroelastic element 140 as it is urgedpast the pinching rollers 192. The rollers 192 fully engage theaeroelastic element 140 and flatten the powder deposited onto theaeroelastic element 140 and break up clumps in the powder.

Thus, the advancement member 162 may be capable of turning the crank torelease the upper clamps and tensioner rods, advancing the dose counter,turning the wheel in the dispensing chute, advancing the spring-loadedaxle in the second spool by one position to advance the aeroelasticelement a predetermined distance from the first spool to the secondspool, and/or moving a dose of powder medicament into the center region142.

Referring again to FIGS. 3A and 3B, according to various aspects, theinhaler 100 may include one or more airflow modifiers 198 proximal ofthe one or more airflow inlets 128 and at a distal end of the centerregion 142. It should be appreciated that the one or more airflowmodifiers 198 may be distal of the center region 142 and/or at a distalportion within the center region 142. In some aspects, the one or moreairflow modifiers 198 may comprise multiple triangular rods extendingfrom the first inner wall 106 to the second inner wall 108. As air flowsthrough the one or more airflow inlets 128 and toward the center region142, the one or more airflow modifiers 198 may cause vortices that allowair to pass above and below the modifiers.

Referring now to FIG. 1, airflow at velocity V over an aeroelasticelement under tension is illustrated. As shown, the airflow may resultin flutter or vibration of the aeroelastic element 140. The vibration isrepresented by vertical arrows, and the airflow is represented byhorizontal arrows. FIG. 2 illustrates the airflow at velocity V past anairflow modifier prior to encountering an aeroelastic element 140. Asshown, the airflow modifier introduces turbulence into the airflow, thusincreasing the vibration or flutter of the aeroelastic element for agiven inhalation strength.

In operation, a method for dispensing powder by inhalation using any ofthe aforementioned exemplary dry powder inhaler apparatuses may beginwith a patient actuating the advancement member. The patient may pursehis/her lips around the mouthpiece and inhales. As the patient inhales,air is sucked into the inhaler through one or more airflow inlets at thedistal end of the inhaler. The inhaled air flows over the airflowmodifiers. The airflow then encounters the aeroelastic element, causingthe element to vibrate or flutter and disperse a dose of powderedmedicament from the element into the airflow. The combined flow of airand powder then flow into the distal end of the airflow nozzle and themouthpiece. The combined flow of air and powder leave the mouthpiece andenter the patient's mouth and respiratory tract. The airflow modifiersand/or the helical shape of the nozzle may increase the turbulence ofthe airflow to better aerosolize and break up the powdered dose ofmedicament into smaller particles, thus maximizing the dose received bythe patient and allowing the smaller particles to pass further into therespiratory tract.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the inhalers and methods ofthe present disclosure without departing from the scope of theinvention. Other embodiments of the invention will be apparent to thoseskilled in the art from consideration of the specification and practiceof the invention disclosed herein. It is intended that the specificationand examples be considered as exemplary only.

1-20. (canceled)
 21. A dry powder inhaler for delivering medicament to apatient, the inhaler comprising: a housing defining a chamber forreceiving a dose of powdered medicament; an inhalation port in fluidcommunication with the chamber; at least one airflow inlet providingfluid communication between the chamber and an exterior of the housing;and a strip of material having a generally flat top surface, a generallyflat bottom surface, and a plurality of recesses in the top surface,wherein the recesses are each configured to hold a metered dosage of apowdered medicament, the strip of material being positioned between theinhalation port and the at least one airflow inlet such that a flow ofair generated by a user via the inhalation port is configured to movethe medicament that is released from one of the recesses through thechamber as an aerosolized dose.
 22. An inhaler as in claim 21, whereinthe recesses are cup shaped in geometry.
 23. An inhaler as in claim 21,wherein the recesses are serially aligned along the strip.
 24. Aninhaler as in claim 21, further comprising an actuator that isactuatable to make contact with the strip of material to therebydisperse the medicament from the recess.
 25. An inhaler as in claim 24,wherein the actuator is actuatable by the user inhalation that causesair to act on the actuator.
 26. The inhaler of claim 24, wherein theactuator comprises an aeroelastic element, and further comprising atleast one tensioning member configured to hold the aeroelastic elementat a tension that produces a desired vibrational response to airflowranges of a patient.
 27. The inhaler of claim 26, wherein the tensioningmember is adjustable to change the desired vibrational response.
 28. Theinhaler of claim 24, wherein the actuator comprises one of a membrane, areed, a sheet, a panel, and a blade.
 29. The inhaler of claim 24,wherein the actuator is made of a material comprising at least one of apolymer, a metal, and a metal-coated polymer.
 30. The inhaler of claim24, further comprising a powder dose applicator, the powder doseapplicator being configured to dispense the dose of powdered medicamentto the recesses prior to inhalation by a patient.
 31. The inhaler ofclaim 21, further comprising: a mouthpiece including the inhalationport; and a nozzle between the chamber and the inhalation port.
 32. Theinhaler of claim 21, wherein the inhalation port is at a first end ofthe housing and said at least one airflow inlet is at a second end ofthe housing substantially opposite the first end of the housing.
 33. Amethod for delivering medicament to a patient comprising: providing aninhaler comprising a housing defining a chamber, an inhalation port influid communication with the chamber, and at least one airflow inletproviding fluid communication between the chamber and an exterior of thehousing; providing a strip of material having a generally flat topsurface, a generally flat bottom surface, and a plurality of recesses inthe top surface, wherein the recesses each hold a metered dosage of apowdered medicament, wherein the strip of material is positioned betweenthe inhalation port and the at least one airflow inlet; and inhalingfrom the inhalation port to draw the medicament that is released fromone of the recesses through the chamber as an aerosolized dose.
 34. Amethod as in claim 33, further comprising contacting the strip todispense the medicament from the recess.
 35. A method as in claim 34,wherein the inhaler includes an actuator, and wherein inhaling from theinhalation port actuates the actuator to contact the strip.
 36. A methodfor metering dosages of a dry powder medicament, the method comprising:providing a strip of material having a generally flat top surface, agenerally flat bottom surface, and a plurality of recesses in the topsurface, wherein the recesses are each configured to hold a metereddosage of a powdered medicament, the strip of material being configuredto be positioned within an inhaler such that a flow of air generated bya user via an inhalation port of the inhaler is configured to aerosolizethe powdered medicament; and using a powder dose applicator, dispensinga dose of powdered medicament to the recesses.
 37. A method as in claim36, wherein the powder dose applicator comprises a dispensing chutehaving a top end and a bottom end, and a wheel at the bottom end, andfurther comprising rotating the wheel to dispense the powder from thebottom end and into one of the recesses.
 38. A method as in claim 36,wherein the recesses are cup shaped in geometry.
 39. A method as inclaim 36, wherein the recesses are serially aligned along the strip, andfurther comprising advancing the strip and dispensing powder into thenext recess.